Psychiatric disorders and cognitive impairment are increasingly being described in patients with vestibular pathology. Yet frameworks that describe the link between emotion, memory and the vestibular system have yet to reach maturity, partly because studies have not yet provided detailed accounts of behavioral changes in experimental animals, or in man. One of the goals of this thesis was to use experimental psychology to define changes in memory and emotional behaviour in rats given bilateral vestibular deafferentation (BVD, n=18) or sham surgery (Sham, n=17). In an elevated-plus maze task, BVD rats made up to 166% greater open arm entries and spent up to 42% more time in the open arms compared to Sham rats. In an elevated-T maze task, BVD rats failed to develop a normal learned inhibition response to open space. In an open field maze BVD rats consistently showed 50-60% greater movement velocity, spent on average 35% more time in the inner most aversive part of the arena, and failed to show the normal boundary-seeking behaviour (thigmotaxis) typical of untreated or Sham rats. In a social interaction test BVD rats spent up to 34% less time engaged in social contact compared to Sham rats. In a hyponeophagia test, BVD rats� latency to eat was 70% greater than Sham rats at 3-weeks post-op., however this difference disappeared at 3- and 5-months. These findings suggest that BVD treatment may in some cases disrupt normal behavioral inhibition. Memory performance was also affected. In a T-maze task BVD rats achieved 40-60% correct arm entries, compared to 90-100% for Sham controls. In a foraging task carried out in darkness, BVD rats� initial homing angle was random, homing paths were ~70% longer, and reference memory errors were ~56% greater compared to Sham rats. To elucidate possible neurochemical substrates for these behavioral changes, western blot assays on monoamine proteins were carried out on tissue from a naïve set of rats (BVD n=6; Sham n=6). In BVD rats, serotonin transporter protein expression was 39% lower in CA1 hippocampus and 27% lower in the forebrain region, despite forebrain tryptophan hydroxylase expression being 34% upregulated. Tyrosine hydroxylase expression in the forebrain region was 27% lower in BVD rats. Proteins related to synaptogenesis were also investigated. In the dentate gyrus SNAP-25 was 37% upregulated in BVD rats, while in area CA2/3 of the hippocampus neurofilament-L was 13% upregulated. Forebrain and entorhinal cortex drebrin expression was 28% and 38% downregulated in BVD rats. Neurofilament-L was also 31% downregulated in the forebrain region of BVD rats. To test whether any of these behavioral or biochemical changes may have been attributable to chronic physiological stress, a corticosterone assay was carried out at the conclusion of behavioral testing; however, the no significant between treatment differences were found. In conclusion, vestibular information appears to be needed for the acquisition of spatial and reference memory as well as the normal expression of emotional behaviour. The neurochemical changes described herein point toward possible substrates for these behaviors, however their full significance has yet to be determined.
| Identifer | oai:union.ndltd.org:ADTP/201524 |
| Date | January 2008 |
| Creators | Goddard, Matthew John, n/a |
| Publisher | University of Otago. Department of Pharmacology & Toxicology |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | http://policy01.otago.ac.nz/policies/FMPro?-db=policies.fm&-format=viewpolicy.html&-lay=viewpolicy&-sortfield=Title&Type=Academic&-recid=33025&-find), Copyright Matthew John Goddard |
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